[Pericardial abscess by aspergillus mimicking a cardiac tumor].

We report a rare case of 34-year-old man who was diagnosed as cardiac tumor after therapy for acute lymphatic leukemia. Echocardiography and computed tomography (CT) showed that the tumor was located from the right atrium to the right ventricle and about 6.0 cm in diameter. Resection of the tumor was performed under cardiopulmonary bypass. The histological findings revealed pericardial abscess by Aspergillus.

Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells.

Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+, CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-, CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57 were positive and three of the seven cases examined for cytoplasmic CD3. Epstein-Barr virus was detected in the tumor cells of 11 of the 13 cases examined. No common cytogenetic abnormalities were identified and 6q anomaly was detected in only one. Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline. Although the overall prognosis was poor with a median survival of 58 days, those who attained remission showed better prognosis (P=0.005). These findings suggest that ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations. Intensive treatment for ANKL may result in a better prognosis.

Chronic methamphetamine administration inhibits cerebral ischemia-induced hyperactivity in Mongolian gerbils.

The effect of single and chronic methamphetamine (MAP) administration on ischemia-induced hyperactivity was investigated and the mechanism of ischemia-induced hyperactivity was discussed. Ischemia-induced hyperactivity was recognized 3 h after ischemia. However, ischemia-induced hyperactivity at 1 day after ischemia was inhibited when MAP, in a dose of 10 mg/kg, was administered for 7 days and withdrawn for 7 days. It was reported that MAP treatment caused an irreversible decrease in the number of dopamine (DA) uptake sites. In addition to this, monoamine oxidase and the uptake of DA into the nerve terminals are disturbed by cerebral ischemia. Therefore, a lot of DA release happened during and immediately after ischemia, and a marked down-regulation of DA receptor occurred 24 h after ischemia in MAP-injected group. It is conceivable that the DA receptor, especially the presynaptic DA uptake site, is related to the occurrence of ischemia-induced hyperactivity. Further studies appear to be necessary to clarify acceptor susceptibility when neurotransmitters are normalized after transient ischemia.

Light conditions during sleep period and sleep-related lifestyle in Japanese students.

The effects of light conditions during night sleep on sleep habits and morning-evening preference were studied in Japanese students (18-28 years old). Students who usually used fluorescent or non-fluorescent light on the room ceiling, wall or desk preferred to have a daytime nap significantly later (Mean: 14:50 h) than those who used no light (13:34 h). Students who used no curtain or a half-transparent lace-curtain showed shorter sleep latency (duration from going-to-bed to sleep-onset) than those who used a curtain which shuts off lights from outside. Light conditions during the middle of night and early in the morning may affect the timing of sleep in Japanese students based on the circadian system.

[Pure red cell aplasia developing during the course of primary macroglobulinemia associated with pseudochylothorax and IgA nephropathy].

A 74-year-old man who had undergone artificial pneumothorax therapy for pulmonary tuberculosis 40 years earlier was admitted because of blurred vision, headache, and numbness of the lower limbs in October 1997. He presented with anemia and leukocytopenia with monoclonal gammopathy of IgM (kappa). His bone marrow was diffusely infiltrated with small lymphocytes, plasmacytoid lymphocytes, and plasma cells expressing IgM, kappa surface immunoglobulin. On the basis of these findings, primary macroglobulinemia (PMG) was diagnosed. CT scan of the chest demonstrated pleural effusion of the right lung encapsulated in a thickened pleura, and pseudochylothorax was diagnosed from a specimen of chyliform fluid which contained numerous cholesterol crystals and was positive for Mycobacterium tuberculosis (MT) on PCR assay. The patient's condition was also complicated by chronic renal failure due to IgA nephropathy, which may have been a consequence of the tuberculosis, possibly due to an abnormal IgA-mediated immune response to MT. The patient gradually developed pure red cell aplasia during the course, probably due to an autoimmune mechanism. Later in the course, immunoglobulin gene analysis of the malignant cells of PMG showed that they were derived from antigenically selected cells. In the context of antigenic stimulation, the role of MT antigen in the pathogenesis of PMG was of interest in this patient.

Clinicopathological study on eyes from cases of Fukuyama type congenital muscular dystrophy.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder characterized by progressive muscular dystrophy and dysgenesis of the central nervous system and eyes. To clarify the pathomechanism of the ocular involvement in FCMD, we performed postmortem pathological analyses of eyes from three postnatal FCMD cases, two fetal FCMD cases, and three control cases by macroscopic, histopathological, immunohistochemical and in situ hybridization approaches. The macroscopic and histopathological examinations revealed a variety of ocular abnormalities such as folding, fusion or dysplasia of the retinas in the FCMD cases both with and without ophthalmological alterations. Immunoreactivities for collagen IV and laminin, produced by Müller cells, as the basement membrane components, were less intense in the inner limiting membrane of the FCMD retinas than in that of the control retinas. A number of the perivascular glial cells containing S-100 protein and glial fibrillary acidic protein were increased in the postnatal FCMD cases. Immunoreactivities for vimentin, glutamate transporter-1, glutamine synthase and ornithine aminotransferase, expressed in the Müller cells, were undetectable in the fetal FCMD retinas, and reduced in the postnatal FCMD retinas compared with the control retinas. Fukutin mRNA signals were distributed diffusely in the retinoblast layer of the control retinas, focally in the retinoblast layer of the fetal FCMD retinas, and only in the dysplastic areas with rosette formation of the postnatal FCMD retinas, composed of retinoblasts and other retinal cells including the Müller cells. The present findings suggest that the Müller cells are implicated in the retinal pathology of FCMD.

A pathogenic point mutation reduces stability of mitochondrial mutant tRNA(Ile).

Point mutations in mitochondrial tRNA genes are responsible for individual subgroups of mitochondrial encephalomyopathies. We have recently reported that point mutations in the tRNA(Leu)(UUR) and tRNA(Lys) genes cause a defect in the normal modification at the first nucleotide of the anticodon. As part of a systematic analysis of pathogenic mutant mitochondrial tRNAs, we purified tRNA(Ile) with a point mutation at nucleotide 4269 to determine its nucleotide sequence, including modified nucleotides. We found that, instead of causing a defect in the post-transcriptional modification, a pathogenic point mutation in the mitochondrial tRNA(Ile) reduced the stability of the mutant tRNA molecule, resulting in a low steady-state level of aminoacyl-tRNA. The reduced stability was confirmed by examining the life-span of the mutant tRNA(Ile) both in vitro and in vivo, as well as by monitoring its melting profile. Our finding indicates that the mutant tRNA(Ile) itself is intrinsically unstable.

Reactions of grignard reagents with bis- or mono-phosphonium ions in situ generated from Bu3P and dicarboxylic acid dichlorides or omega-ethoxycarbonyl alkanoyl chlorides as a novel method to obtain diketones and ketoesters.

Reactions of Grignard reagents with bis-phosphonium or mono-phosphonium ions in situ generated from BusP and ClCO(CH2)nCOCl (5) or ClCO(CH2)nCO2Et (13) as a tool for preparation of symmetrical diketones or ketoesters were examined. Addition of Bu3P (2.0 eq) to a THF solution of 5 (n=2) at -40 degrees C followed by addition of n-BuMgCl (2.0 eq) gave the corresponding diketone in good yield. When a mixture of BusP and the Grignard reagent (2.0 eq each) was added to the dichloride solution at the same temperature, a better result was obtained. The latter method not with PhMgBr but with n-BuMgCl or MeMgBr was shown to be useful for preparation of symmetrical alkanediones and keto alkanoates from various 5 (n=2-6) and 13 (n=2 or 3), respectively. For synthesis of alpha-diketones or alpha-ketoesters, only PhMgBr entered the reaction, although the yields were not satisfactory. Addition of a mixture of Bu3P (2.0 eq), MeMgBr (1.0 eq) and BuMgCl (1.0 eq) to a THF solution of 5 (n=4) at -40 degrees C afforded a mixture of 2,7-undecanedione and the corresponding two symmetrical diketones, with the yield of the unsymmetrical diketone being 36%.

Effect of calcium channel blockers on cerebral ischemia-induced hyperactivity in Mongolian gerbils.

When both common carotid arteries of Mongolian gerbils were occluded for 5 min to produce ischemic insult, locomotor activity was increased the following day. The effect of calcium channel blockers on this ischemia-induced hyperactivity was investigated. Nimodipine, at doses of 5, 10, and 20 mg/kg, dose dependently and significantly decreased ischemia-induced hyperactivity. Nicardipine significantly decreased ischemia-induced hyperactivity and doses of 10 and 20 mg/kg. Nifedipine and flunaridine also significantly decreased ischemia-induced hyperactivity at doses of 20 mg/kg. Verapamil had no effect on ischemia-induced hyperactivity at a dose of 20 mg/kg. These findings suggest that ischemia-induced hyperactivity is related to calcium channels. These relationship between calcium channels and dopaminergic function is discussed.

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation support in a patient with breast cancer metastasis to bone marrow: immunocytochemical monitoring of cancer-cell contamination].

A 32-year-old woman who 1 year earlier underwent a right mastectomy for stage II breast cancer with the histology of invasive ductal carcinoma (scirrhus type) was admitted due to recurrent, metastatic breast cancer in January 1997. She presented multiple metastatic lesions in the skin, lymph nodes, bone, lungs, liver, and spleen, and her bone marrow was replaced almost entirely by tumor cells. The patient was sequentially treated with 5 courses of cyclophosphamide (CPA) and adriamycin (ADM) (CA); 2 courses of CPA, ADM, and 5-fluorouracil; 5 caurses of docetaxel hydrate; and 1 course of CA. After recovery of the normal bone marrow by standard-dose chemotherapies, peripheral blood stem cells (PBSC) were then collected after mobilization with G-CSF. The number of breast cancer cells in bone marrow and PBSC samples was determined by immunocytochemical staining with an anti-cytokeratin monoclonal antibody. The number of tumor cells in PBSC sample was within the level for non-metastatic breast cancer. Complete remission was obtained with high-dose chemotherapy consisting of CPA and Thio-TEPA, and supported by autologous PBSC transplantation.

Multiple liver metastases of breast cancer: report of a case successfully treated with hormone-cytokine-chemotherapy.

The prognosis of patients with hepatic metastasis from breast cancer is usually extremely poor. We present the case of a 39-year-old Japanese woman diagnosed with multiple liver metastasis from breast cancer. A novel approach consisting of hormone-cytokine-chemotherapy with an arterial infusion therapy was carried out. Computed tomography and ultrasonography revealed that the multiple liver metastases were reduced with remaining calcification. Tumor markers decreased rapidly. Complete regression was achieved after these treatments. To date, there has been no relapse during the 8-year follow-up period. These results suggest that the hormone-cytokine-chemotherapy might be a rational modality of treatment against multiple metastatic breast cancer.

[Splenic lymphoma with villous lymphocytes expressing chromosomal abnormalities].

An 88-year-old Japanese woman with splenomegaly, but without lymphadenopathy, was admitted because of epigastric distress. Laboratory data disclosed an RBC of 310 x 10(4)/microliter, Hb of 10.1 g/dl, Ht of 30.6%, Plt count of 9.8 x 10(4)/microliter, and WBC of 4,470/microliter with 38% abnormal lymphocytes. Peripheral blood films revealed lymphocytes with thin, short cytoplasmic villi, condensed nuclear chromatin, and small nucleoli. The lymphocytes stained negative for tartrate-resistant acid phosphatase. Also, immunophenotyping was positive for expression of the cell surface markers CD19, CD20, IgG, kappa and HLA-DR, but not for CD5, CD10, CD11c, CD23, CD25, CD38, or CD103 antigens. Chromosomal analysis of peripheral blood cells disclosed the 46, XX, del(7), (q32) aberration. A splenectomy was performed simultaneously with partial colon resection because of a mucinous carcinoma found in the transverse colon. Histologic examination of resected spleen tissues revealed a distinctive pattern of white pulp infiltration by lymphoma cells. The histologic findings and clinical data were consistent with the features of splenic lymphoma with circulating villous lymphocytes. Our patient exhibited a relatively benign clinical course, and was being followed on an outpatient basis with no additional therapy.

Effect of dopamine blockers on cerebral ischemia-induced hyperactivity in gerbils.

When common carotid arteries of Mongolian gerbils were clamped for 5 min, locomotor activity significantly increased the day after the ischemic insult. This hyperactivity induced by cerebral ischemia was evident in both light and dark periods. The significant increases in locomotor activity seen in both periods were noted for 3 and 9 days after occlusion, respectively. Effects of dopamine receptor antagonists on the ischemia-induced hyperactivity were investigated the day after the ischemia insult. Haloperidol, sulpiride, and eticlopride, all dopamine D2 receptor antagonists, decreased the ischemia-induced hyperactivity at doses that had no effects on locomotor activity in sham-operated animals. SCH23390, a dopamine D1 receptor antagonist, had no clear effects on the ischemia-induced hyperactivity. Clozapine, with not so high an affinity for the dopamine D2 receptor decreased the ischemia-induced hyperactivity when given in a relatively high dose. Thus, the ischemia-induced hyperactivity is apparently related to abnormalities in dopaminergic functions, particularly the dopamine D2 receptor.

High frequency expressions of CD44 standard and variant forms in non-small cell lung cancers, but not in small cell lung cancers.

BACKGROUND AND OBJECTIVES: Organ specificity has been demonstrated in the mode of CD44 expression among several cancers. METHODS: We examined the expressions of CD44 standard (CD44s) and CD44 variants (CD44v) in 14 cell lines (small cell lung cancer (SCLC): 5, non-small cell lung cancer (NSCLC): 9 and 20 surgically resected samples (SCLC: 7, NSCLC: 13) of lung cancer using reverse transcription polymerase chain reaction and immunohistochemistry. RESULTS: Although both NSCLC and SCLC expressed CD44s, the frequency and intensity of CD44s expression in NSCLC were different from those in SCLC: cell lines, 89% vs. 40%; tumor samples, 100% (diffusely stained) vs. 57% (focally stained). CD44s expression was partially or completely repressed in SCLC. However, NSCLC frequently expressed CD44v, but SCLC expressed infrequently: cell lines, 67% vs. 20%; tumor samples, 69% vs. 0%. The N-417 line, which only expressed some CD44v in SCLC, falls SCLC and NSCLC both in biomarkers and in growth patterns. CONCLUSIONS: CD44 expression was repressed in SCLC but was enhanced in NSCLC.

Radiographic features of an aneurysmal bone cyst of the orbit.

Aneurysmal bone cyst is an unusual benign solitary lesion of bone occurring rarely in the orbit. In this report, we present computed tomography and magnetic resonance images of an orbital aneurysmal bone cyst involving the frontal bone in a 16-month-old boy. The aneurysmal bone cyst exhibited bone destruction, new bone formation of the orbital roof and fluid-fluid levels in the lesion following hemorrhage. These radiographic features may be useful for diagnosing orbital aneurysmal bone cysts.

Expression of alpha-fetoprotein and albumin genes in human hepatocellular carcinomas: limitations in the application of the genes for targeting human hepatocellular carcinoma in gene therapy.

For an approach of gene therapy for hepatocellular carcinoma (HCC), transcriptional regulatory sequence (TRS) of either alpha-fetoprotein (AFP) or albumin has been used for targeting cancer cells. To examine the feasibility of using TRSs of these genes for possible gene therapy of HCCs, the cellular distribution of AFP and albumin gene transcripts was studied in 25 cases of surgically removed human HCCs. AFP gene expression was observed in HCC nodules of 13 cases. The expression in HCC was heterogeneous, and the distribution of the transcripts was mostly sparse and spotty. The higher the serum AFP levels, the larger population of the AFP-expressing HCC cells tended to reflect. In noncancerous liver, a slight AFP expression was found by Northern blot analysis, but the transcripts were not detected in the liver sections. In contrast, albumin expression was found in all HCCs as well as in noncancerous hepatocytes. In HCC, the transcripts for albumin were distributed in cancer cells, and the expression varied with nodules. There were more albumin-expressing cancer cells than the AFP-expressing cells. Albumin expression was retained even in poorly differentiated HCC, although the intensity of the signal was not as strong as in more-differentiated HCCs. Metastatic HCC nodules revealed transcripts for both AFP and albumin genes, and those were clearly recognized in the lung tissue. These results suggest that, for gene therapy for HCCs, neither AFP nor albumin are ideal options for targeting HCC cells. AFP-TRS may be used as a transcriptional regulator in selected cases in which AFP gene expression is observed in the cancer nodules. The serum AFP level appears to be an important indicator in selecting cases. Albumin-TRS in conjunction with retroviral vector might be used in limited cases such as HCCs with no AFP expression. However, careful consideration must be taken, because albumin is constitutively expressed in normal hepatocytes, and AFP-expressing nonmalignant progenitor cells possibly exist.

Mutations of the p53 gene in human lung cancer from chromate-exposed workers.

We examined p53 mutations in 20 cancer samples from 19 chromate workers with lung cancer by Polymerase chain reaction-Single strand conformation polymorphism analysis and direct sequencing. Six missense mutations were identified in 4 (20%) of the 20 chromate lung cancer samples. Fewer mutations were found in the patients with lung cancers who had been exposed to chromate than in those who had not. However, the pattern of p53 mutations in lung cancer patients exposed to chromate differed from that of common lung cancers in 3 respects. There were no apparent G to T transversions, which are common base changes in lung cancers. Half of the mutational sites (3/ 6) had changes of AT base-pairs, and 2 of 4 mutational tumor samples had double missense mutations. Our results suggested that chromate exposure may induce point mutation of the p53 gene.

The expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer.

Recently, it was suggested that splice variants of the surface glycoprotein CD44 (CD44v) were associated with tumor metastasis in some cancers. We examined the expression of variant forms of CD44 in 31 non-small cell lung carcinomas (NSCLCs) and in 8 normal lung tissue samples by reverse transcription-PCR (RT-PCR). CD44v3, CD44v5, CD44v6, and CD44v7 were not expressed or were weakly expressed in normal lung tissue (0 of 8). In contrast, CD44v3, CD44v5, CD44v6, or CD44v7 was expressed in 28 of 31 (90.3%) NSCLCs. Additionally, we examined the expression of CD44v6, which has been shown to be related to metastasis, in 5 normal lungs and 30 NSCLCs by RT-PCR and immunohistochemical analysis to clarify which cells express CD44v6 in NSCLC specimens. Thirty-six of 61 (59%) NSCLCs variably expressed CD44v6 by RT-PCR, and cancer cells were selectively immunostained by anti-CD44v6 antibodies in 23 of 30 (76.7%) NSCLCs. The results of immunohistochemical analysis almost correlated with those of RT-PCR. NSCLCs with lymph node metastasis expressed significantly more v6 exon than did those without lymph node metastasis [23 of 29 (79.3%) versus 13 of 32 (40.6%); P < 0.01]. There was a significant association between the intensity of v6 expression by RT-PCR and the frequency of cases showing lymph node metastasis (Cochran-Armitage's test, P < 0.002). In conclusion, this study demonstrated that in NSCLC, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC.